ABSTRACT The 2014 Surgeon General Report (SGR) concluded that there has been an unanticipated increase in lung adenocarcinomas, now the most common type of lung cancer. The SGR identified ventilation in cigarette filters, a design introduced in the 1960s and an important way to lower machine measured cigarette tar yields, as a potential contributor to the increase in these lung cancers. In a recent review, we found highly suggestive evidence that filter ventilated cigarettes was the cause of the increased incidence of adenocarcinoma lung cancer and concluded that there was enough evidence for the FDA to consider regulating filter ventilation, including a ban. Independent of the risk for adenocarcinoma, there would be sufficient justification for regulation based on the impact of ventilation on harmful constituent yields, smoking behavior and smokers' misperception of health risks. However, prior to any regulatory action, the consequences of such a ban needs to be studied. This P01 describes a set of systematic and comprehensive studies that examines the toxicity, appeal and abuse liability of unventilated filters as compared to ventilated filters in the context of a marketplace with and without alternative nicotine delivery systems (ANDS). Four integrated projects and three cores are proposed and involve a team of multi-disciplinary investigators who have worked together in developing validated models and measures to test tobacco products. The four projects address 1) how unventilated vs. ventilated cigarettes are smoked and the resulting carcinogen exposure levels and potential harm when used with and without ANDS (Project 1); 2) the relative abuse liability of these ventilated vs. unventilated cigarettes and the extent to which ANDS serves as a substitute for unventilated cigarettes (Projects 2 and 3); and 3) the effects of ventilation and product packaging/messaging on consumer perceptions of harm, response and uptake and how these perceptions can be modified by ANDS (Project 4). This research is novel in many ways, including the first to assess the impact of removing filter ventilation and doing this in the context of a complex tobacco marketplace. The projects that we propose are highly integrated. None of these studies alone can address the population impact of a ban on ventilation. It is the combination of these complementary studies that can address the impact of a ban on toxicity, uptake and intensity of product use to determine population health impact. The results of this study would provide critical information to the U.S. Food and Drug Administration on whether or not a ban would lead to improved public health.